This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Plasmodium, causative agents of malaria, exhibit cell traversal activity as a prelude to an obligatory developmental stage in hepatocytes and onset of malarial symptoms. Disruption of the Sporozoite Protein Essential for Cell Traversal-1 (SPECT1) gene in the early infection stage of Plasmodium (sporozoite) decreases cell traversal activity and reduces hepatocyte infection. Thus SPECT1 is a potential target for vaccine development. Here we propose to assist with malarial vaccine development and determining the molecular mechanism of SPECT1 function by solving its x-ray crystal structure. Another project focuses on solving crystal structures of proteins involved in the assembly and function of the type three secretion system (TTSS) in bacteria. TTSS forms an injectosome through which effectors and toxins pass from the bacterial cytosol to host cells. The system is being extensively studied in our lab using Yersinia pseudotuberculosis as a model.An additional project examines diversity-generating retroelements (DGR) which produce massive sequence variability in ligand-binding proteins for proper infection by Bordetella bacteriophage. Our goal is to understand how DGR-encoded variable proteins accommodate massive sequence variation and recognize diverse targets.